Chronic Granulomatous Disease (CGD: An Update on Pathogenesis and Management for Internists

Reinhard A. Seger

Abstract

Inborn errors of immunity are emerging in the medical

practice of adult physicians. The median life expectancy of once fatal pediatric primary immunodeficiencies (PIDs) was extended into adulthood by increasing awareness , shortening diagnostic delays and developing modern treatment regimens, incl. hemopoietic stem cell transplantation (HSCT). A prime example of the impressive progress is chronic granulomatous disease (CGD), an inherited deficiency of the innate immune system, with a median patient survival of 40 years and more.

The last few years have witnessed four major advances in our knowledge of CGD:

Realization of an increased burden of inflammatory complications in adult life requiring specialist medical care.

Better understanding of the physiologic anti-inflammatory function of the defective NADPH system opening new avenues for targeted drug interventions

Advances in reduced intensity conditioning (RIC) for allogeneic HSCT making it a safe procedure even for patients with severe infection or hyperinflammation.

Encouraging early data of an ongoing trial of gene-replacement therapy using a self-inactivated lentiviral vector.